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Aggregatibacter actinomycetemcomitans – a periopathogen with capacity to cause dysregulation in the host response

Research project Periodontitis is an infection induced inflammatory disease that cause degradation of the tooth supporting tissues. Carriers of highly leukotoxic A. actinomycetemcomitans are at high risk for onset and progression of aggressive forms of periodontitis. The pro-inflammatory effect induced by leukotoxin on human macrophages might be crucial for the rapid tissue destruction often seen in vicinity to an A. actinomycetemcomitans periodontal infection.

Aggregatibacter actinomycetemcomitans is a facultative anaerobe periodontal pathogen associated with aggressive forms of periodontitis and systemic complications, like endocarditis and atherosclerosis. It is suggested that this bacterium colonizes the oral mucosa early in life and live as a commensal without causing any harm to the carrier. Later in life A. actinomycetemcomitans can be translocated to the gingival crevice where the infection can cause loss of the tooth supporting tissues, connective tissue and bone. In addition, the oral mucosa can be a reservoir for this bacterium also for systemic translocation. There is a great genetic diversity within this bacterial specie and certain genotypes are more prone to cause disease than other. A. actinomycetemcomitans expresses a pore forming protein (leukotoxin) that selectively kills human leukocytes. A certain genotype of this bacterium (JP2) with enhanced production of leukotoxin (LtxA) has an extraordinary strong association to the onset of aggressive forms of periodontitis in the infected individual. In addition, a recent finding has linked the activity of leukotoxin to presence of autoantibodies (CCP) that are risk markers rheumatoid arthritis. The aims of the present study is to examine the role of A. actinomycetemcomitans and its different genotypes as a risk marker for initiation and progression of aggressive forms of periodontitis, as well as the rheumatoid arthritis associated autoantibodies.

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Project overview

Project period

2017-01-01 2020-12-31

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Project description

The findings from the present program may contribute to new therapeutic strategies for prevention of periodontitis and related systemic health effects. Specifically we will 1) study the role A. actinomycetemcomitans for the outcome of periodontal treatment in a study population with chronic periodontitis, as well as to examine the presence of systemic antibodies to LtxA and CCP during the intervention period 2) examine the importance of different genetic variants of A. actinomycetemcomitans in relation to virulence expression, disease association and dissemination 3) examine the exosomes released from LtxA exposed macrophages in regards to its protein profile and its ability to transfer inflammation or induce CCP production 4) evaluate tools for virulence blocking that could be used in new therapeutic strategies for aggressive forms of periodontitis. Our general goal is that relevant genetic markers for virulent A. actinomycetemcomitans will be used as a diagnostic tool and that a complete understanding of LtxA induced inflammation provides targets for new specific therapeutic agents. These new preventive strategies will hopefully keep the prevalence of aggressive forms of periodontitis low in Sweden, as well as the systemic negative health effect associated with periodontal infections